The long term goals of this research are to understand how the cardiovascular system adjust to normal pregnancy and ultimately, how these adjustments relate to the clinical syndrome of pregnancy-induced hypertension (PIH). In this proposal, the hypotheses to be tested are that pregnancy is associated with an increase in lipid hydroperoxide formation which is further elevated in pregnancy-induced hypertension and results in the alteration of the normal function of the endothelium both in the maternal and placental vasculature. This alteration in function consists of a reduction in vascular prostacyclin production as well as endothelial-derived relaxing factor(s). This results in an increased in vascular reactivity and modification of the normal decrease in mean maternal arterial pressure observed during gestation. We will use a pregnant and nonpregnant rat model of chronically elevated lipid hydroperoxides to examine blood pressure and vascular reactivity in vivo. Mesenteric arteries from these same animals will be studied in vitro for their endothelial-dependent and independent relaxation responses as well as PGI2 production using two myograph systems designed for studying resistance size vessels. An increase in endothelial-mediated relaxation responses during pregnancy will be demonstrated in tissue from pregnant rats as well as human rectus perforator arteries and fetal placental arteries. The integrity of this relaxation response and the ability to produce PGI2 will be compared between these vessels from normal pregnancies and from women with PIH. Lipid hydroperoxide levels in the plasma will be measured longitudinally during normal human pregnancy and those at risk for PIH using a precise high pressure liquid chromatography assay method. These levels will be correlated to standard assessments of lipid peroxide mediated damage as well as to clinical outcome data including accurate morphometric parameters in the placentae and neonates. Finally, placentae from normal and PIH pregnancies will be examined for their lipid hydroperoxide in the basal and stimulated state.